3-66251482-A-G

Variant names:

• chr3-66251482-A-G
• rs13076104
• NM_001379210.1:c.300+8170A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001379210.1(SLC25A26):​c.300+8170A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 152,124 control chromosomes in the GnomAD database, including 3,941 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.22 (3941 hom., cov: 32)
• Consequence: SLC25A26 NM_001379210.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.60
• Publications: 7 publications found

Genes affected

SLC25A26 (HGNC:20661): (solute carrier family 25 member 26) This gene is a member of the mitochondrial carrier family which includes nuclear-encoded transporters localized on the inner mitochondrial membranes. Members of the family transport important small molecules across the mitochondrial inner membrane. This protein is involved in the transport of S-adenosylmethionine (SAM) into the mitochondria. Mutations in this gene are associated with combined oxidative phosphorylation deficiency 28. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2017]

SLC25A26 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• combined oxidative phosphorylation deficiency 28

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A26	NM_001379210.1	c.300+8170A>G		intron_variant	Intron 3 of 9	ENST00000354883.11	NP_001366139.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A26	ENST00000354883.11	c.300+8170A>G		intron_variant	Intron 3 of 9	2	NM_001379210.1	ENSP00000346955.6

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32888 AN: 152006 Hom.: 3931 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.352

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.206

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.216 AC: 32929 AN: 152124 Hom.: 3941 Cov.: 32 AF XY: 0.220 AC XY: 16359 AN XY: 74364

African (AFR) AF: 0.123 AC: 5119 AN: 41506

American (AMR) AF: 0.279 AC: 4264 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 577 AN: 3466

East Asian (EAS) AF: 0.155 AC: 804 AN: 5178

South Asian (SAS) AF: 0.118 AC: 571 AN: 4820

European-Finnish (FIN) AF: 0.352 AC: 3720 AN: 10568

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.252 AC: 17136 AN: 67982

Other (OTH) AF: 0.203 AC: 429 AN: 2114

Alfa AF: 0.239 Hom.: 2258

Bravo AF: 0.210

Asia WGS AF: 0.150 AC: 521 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.012
DANN	Benign	0.23
PhyloP100		-2.6

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs13076104; hg19: chr3-66301906;